title: Associated risk of recombinant activated factor VIIa application.
abstract: BACKGROUND
  The recombinant human coagulation FVIIa was approved for the treatment of bleeding in hemophilia patients. The reports of a good hemostatic effect were followed by studies and applications without a regulatory extension of the therapeutic indication (off-label use). The aim of this retrospective study is the evaluation of thromboembolic adverse events and side effects in a large cohort of patients with FVIIa therapy.
  
  
  METHODS
  In the period from January 2009 to March 2011, a total of 143/2453 (5.8%) cardiac surgical patients (69% male; age 67 ± 11 years; 39% thoracic aorta) were treated with different doses (mean, 6.1 mg; range, 1 to 27.2 mg) of factor VIIa. The administration of FVIIa was seen as a last therapeutic option and administered at the end of the treatment algorithm for severe bleeding.
  
  
  RESULTS
  Due to an acute bleeding situation in 143 patients, 7.9 ± 5.8 units of packed red blood cells, 9.5 ± 6.1 units of fresh frozen plasma, 1740 ± 1860 IU PPSB (Prothrombin-Proconvertin-Stuart Factor-Antihemophilic Factor B), 5.6 ± 4 g fibrinogen, and 7.9 ± 7.6 units of platelets were administered. A re-thoracotomy was necessary, despite maximal procoagulant therapy, in 55% of patients. The in-hospital mortality was 36% (51/2453 = 2%). Thrombotic complications occurred with a frequency of 16% (mesenteric infarction, n = 9; stroke/transient ischemic attack, n = 3; myocardial infarction, n = 3; other, n = 8).
  
  
  CONCLUSIONS
  The proof of direct causality of the events in relation to the administration of FVIIa is difficult because the temporal and therapeutic relationships with concomitant vasoconstrictive and procoagulant therapies were not obvious. However, there remains a suspicion that a higher rate of mesenteric infarctions may be provoked by the administration of FVIIa.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Johann Wolfgang Goethe University, 60590 Frankfurt am Main, Germany. cardiac.surgeon@dr-kiessling.com
authors.forename: Arndt-Holger
authors.initials: AH
authors.lastname: Kiessling
authors.forename: Janine
authors.initials: J
authors.lastname: Nitsch
authors.forename: Ulrich
authors.initials: U
authors.lastname: Strouhal
authors.forename: Angela
authors.initials: A
authors.lastname: Kornberger
authors.forename: Andreas
authors.initials: A
authors.lastname: Zierer
authors.forename: Anton
authors.initials: A
authors.lastname: Moritz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D013504:Cardiovascular Surgical Procedures / Q000401:mortality*; D003029:Coagulants / Q000627:therapeutic use; D015897:Comorbidity; D064420:Drug-Related Side Effects and Adverse Reactions / Q000401:mortality*; D015942:Factor VIIa / Q000627:therapeutic use*; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007238:Infarction / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000401:mortality* / Q000517:prevention & control*; D015995:Prevalence; D012189:Retrospective Studies; D018570:Risk Assessment; D016019:Survival Analysis; D015996:Survival Rate; D013927:Thrombosis / Q000401:mortality*; D016896:Treatment Outcome
chemical_list: D003029:Coagulants; D015942:Factor VIIa